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  • Original Paper
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Distinct methylation patterns of two APC gene promoters in normal and cancerous gastric epithelia

Oncogene volume 19, pages 3642–3646 (2000)Cite this article

Abstract

The adenomatous polyposis coli (APC) tumor suppressor gene is mutationally inactivated in both familial and sporadic forms of colorectal cancers. In addition, hypermethylation of CpG islands in the upstream portion of APC, a potential alternative mechanism of tumor suppressor gene inactivation, has been described in colorectal cancer. Because a subset of both gastric and colorectal cancers display the CpG island methylator phenotype, we hypothesized that epigenetic inactivation of APC was likely to occur in at least some gastric cancers. APC exhibits two forms of transcripts from exons 1A and 1B in the stomach. Therefore, we investigated CpG island methylation in the sequences upstream of exons 1A and 1B, i.e., promoters 1A and 1B, respectively. We evaluated DNAs from 10 gastric cancer cell lines, 40 primary gastric cancers, and 40 matching non-cancerous gastric mucosae. Methylated alleles of promoter 1A were present in 10 (100%) of 10 gastric cancer cell lines, 33 (82.5%) of 40 primary gastric cancers, and 39 (97.5%) of 40 non-cancerous gastric mucosae. In contrast, promoter 1B was unmethylated in all of these same samples. APC transcripts from exon 1A were not expressed in nine of the 10 methylated gastric cancer cell lines, whereas APC transcripts were expressed from exon 1B. Thus, expression from a given promoter correlated well with its methylation status. We conclude that in contrast to the colon, methylation of promoter 1A is a normal event in the stomach; moreover, promoter 1B is protected from methylation in the stomach and thus probably does not participate in this form of epigenetic APC inactivation.

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Acknowledgements

This work was supported in part by a Grant-in-Aid for Cancer Research (No. 10-3) from the Ministry of Health and Welfare of Japan. This work was also supported in part by NIH grants CA85069, CA78843, CA77057, DK47717 and DK53620, and by the Medical Research Service, Department of Veterans Affairs.

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Authors and Affiliations

  1. Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, 990-9585, Yamagata, Japan

    Takashi Tsuchiya, Gen Tamura, Kiyoshi Sato, Yasushi Endoh, Ken Sakata, Zhe Jin & Teiichi Motoyama

  2. Department of Surgery, Yamagata University School of Medicine, 990–9585, Yamagata, Japan

    Osamu Usuba & Wataru Kimura

  3. Department of Microbiology and Molecular Genetics, University of California, Irvine College of Medicine, Irvine, 92697-4025, California, CA, USA

    Satoshi Nishizuka

  4. Department of Medicine, Gastroenterology Division, University of Maryland School of Medicine, 22S Greene Street, Baltimore, 21201, Maryland, MD, USA

    Keith T Wilson, Stephen P James, Jing Yin, A Steven Fleisher, Tongtong Zou, Dehe Kong & Stephen J Meltzer

  5. Department of Pathology, University of Maryland School of Medicine, 22S Greene Street, Baltimore, 21201, Maryland, MD, USA

    Tongtong Zou, Steven G Silverberg & Dehe Kong

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  1. Takashi Tsuchiya
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Tsuchiya, T., Tamura, G., Sato, K. et al. Distinct methylation patterns of two APC gene promoters in normal and cancerous gastric epithelia. Oncogene 19, 3642–3646 (2000). https://doi.org/10.1038/sj.onc.1203704

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